Melatonin production: proteasomal proteolysis in serotonin N-acetyltransferase regulation.
The nocturnal increase in circulating melatonin in vertebrates is regulated by 10- to 100-fold increases in pineal serotonin N-acetyltransferase (AA-NAT) activity. Changes in the amount of AA-NAT protein were shown to parallel changes in AA-NAT activity. When neural stimulation was switched off by either light exposure or L-propranolol-induced beta-adrenergic blockade, both AA-NAT activity and protein decreased rapidly. Effects of L-propranolol were blocked in vitro by dibutyryl adenosine 3',5'-monophosphate (cAMP) or inhibitors of proteasomal proteolysis. This result indicates that adrenergic-cAMP regulation of AA-NAT is mediated by rapid reversible control of selective proteasomal proteolysis. Similar proteasome-based mechanisms may function widely as selective molecular switches in vertebrate neural systems.
Gastel
J A
JA
Section on Neuroendocrinology, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD 20892-4480, USA.
Roseboom
P H
PH
Rinaldi
P A
PA
Weller
J L
JL
Klein
D C
DC
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008027:Light; D008550:Melatonin / Q000096:biosynthesis*; D009097:Multienzyme Complexes / Q000378:metabolism*; D010870:Pineal Gland / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000502:physiology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D015853:Cysteine Proteinase Inhibitors; D009097:Multienzyme Complexes; D011943:Receptors, Adrenergic, beta; D003994:Bucladesine; D011433:Propranolol; D000242:Cyclic AMP; D001191:Arylamine N-Acetyltransferase; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D008550:Melatonin; D007545:Isoproterenol